Trisubstituted boron-containing molecules
a technology of boron and boron-containing molecules, which is applied in the direction of group 3/13 element organic compounds, drug compositions, chemical treatment enzyme inactivation, etc., can solve the problems of global rise of bacteria and other microorganisms resistant to antibiotics and antimicrobials in general, and pose a major threat, so as to kill or inhibit the growth of bacteria and inhibit the -lactamase
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example 1
G1: (4-Ethyl-1,6-dihydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid
[0430]
Step 1: 5-Ethyl-benzene-1,3-diol
[0431]
[0432]A mixture of 1-(3,5-dihydroxy-phenyl)-ethanone (5 g, 32.89 mmol), 10% Pd—C (1 g) in 4% HCl—H2O (100 mL) was hydrogenated at 1 atmosphere for 16 hours. The mixture was extracted with EtOAc and the organic extracts was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by silica gel flash column chromatography to give 5-ethyl-benzene-1,3-diol (2.37 g, 52%). 1H NMR (400 MHz, CDCl3δ 6.26 (s, 2H), 6.20 (s, 1H), 4.78 (s, 2H), 2.55 (m, 2H), 1.20 (m, 3H).
Step 2: 2-Ethyl-4,6-dihydroxy-benzaldehyde
[0433]
[0434]To a suspension of 5-ethyl-benzene-1,3-diol (2.17 g, 15.72 mmol) and triethyl orthoformate (23.26 g, 157 mmol) in benzene (40 mL) was added AlCl3 (6.30 g, 47.16 mmol) at 0° C. The reaction mixture was stirred at room temperature for 30 minutes. After cooling to room temperature, the mixture was poured onto ice and acidified with HCl. ...
example 2
Testing of Compounds for the Biochemical and Microbial Inhibition of Beta-Lactamases
[1329]Biochemical Inhibition of Beta-Lactamases
[1330]Beta-lactamases CTX-M 9a, KPC-2, SHV-18, TEM-1, TEM-64, AmpC and CMY-2 were used as substrates in in vitro inhibition assays with the compounds of the invention. Beta-lactamases were tested as essentially described by Payne et al., J. Antimicrob. Chemother., 1991; 28: 775-776) with a few modifications. The buffer was 50 mM potassium phosphate pH 7 with 0.2% Triton x-100, and the concentration of nitrocefin was 500 μM for class A β-lactamases and 200 μM for class C β-lactamases. Kinetic data is collected by measuring the rate of change in A486 over 30 minutes. The fraction of enzyme inhibited is determined by dividing the reaction rates in the presence of inhibitor by the reaction rate determined in the absence of inhibitor. Dose-response curves are then generated by plotting log [inhibitor] vs. fraction inhibited. IC50 values were determined from t...
example 3
Antibacterial MIC Testing
[1397]All MIC testing of bacteria followed the Clinical and Laboratory Standards Institute (CLSI) guidelines for antimicrobial testing of aerobic bacteria (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Seventh Edition)(M07-A7) and anaerobic bacteria (Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—Seventh Edition) (M11-A7). The bacteria against with MIC data for exemplary compounds of the invention are provided in FIG. 1.
[1398]It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety...
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